Grill Jessica I, Neumann Jens, Hiltwein Felix, Kolligs Frank T, Schneider Marlon R
Institute of Molecular Animal Breeding and Biotechnology, Gene Center, University of Munich, Feodor-Lynen-Str. 25, 81377, Munich, Germany.
Dig Dis Sci. 2015 Apr;60(4):895-902. doi: 10.1007/s10620-015-3551-x. Epub 2015 Jan 30.
E-cadherin is a cell adhesion protein with crucial roles in development, tissue homeostasis, and disease. Loss of E-cadherin in the adult intestinal epithelium disrupts tissue architecture and is associated with impaired localization and function of goblet and Paneth cells, reduced expression of antibacterial factors, and deficiency in clearing enteropathogenic bacteria. Several studies have suggested a role of E-cadherin in human inflammatory bowel disease.
To investigate the role of E-cadherin deficiency in the pathogenesis of inflammatory bowel disease in a mouse model of experimentally induced colitis.
To induce E-cadherin deficiency, Villin-Cre-ER (T2) ;Cdh1 (fl/fl) mice received intraperitoneal injections of tamoxifen at days 1, 2, 5, and 8. Experimental colitis was induced by oral administration of dextran sodium sulfate (DSS, 3.5 % in the drinking water) for 3 days, starting at the third day after the first tamoxifen injection.
E-cadherin deficiency in the adult mouse intestinal epithelium aggravates the clinical and histological features of DSS-induced colitis. Upon DSS treatment, mice deficient in E-cadherin lost more weight, were more severely dehydrated, and showed more frequently blood in the feces. Histologically, intestinal E-cadherin deficiency was associated with exacerbated acute and chronic inflammation and increased regenerative epithelial changes. Finally, the changes in the epithelium were distributed more diffusely in E-cadherin-deficient mice, while the mucosal damage was more focally localized in control animals.
Our findings suggest that E-cadherin may play an important role in the pathogenesis of ulcerative colitis, one of the major clinical forms of inflammatory bowel disease.
E-钙黏蛋白是一种细胞黏附蛋白，在发育、组织稳态和疾病中发挥着关键作用。成年肠道上皮细胞中E-钙黏蛋白的缺失会破坏组织结构，并与杯状细胞和潘氏细胞的定位及功能受损、抗菌因子表达降低以及清除肠道病原菌能力不足有关。多项研究表明E-钙黏蛋白在人类炎症性肠病中发挥作用。
在实验性诱导结肠炎的小鼠模型中研究E-钙黏蛋白缺乏在炎症性肠病发病机制中的作用。
为诱导E-钙黏蛋白缺乏，在第1、2、5和8天给Villin-Cre-ER（T2）;Cdh1（fl/fl）小鼠腹腔注射他莫昔芬。从首次注射他莫昔芬后的第三天开始，通过口服给予葡聚糖硫酸钠（DSS，饮用水中浓度为3.5%）3天来诱导实验性结肠炎。
成年小鼠肠道上皮细胞中E-钙黏蛋白缺乏会加重DSS诱导的结肠炎的临床和组织学特征。在DSS治疗后，E-钙黏蛋白缺乏的小鼠体重减轻更多、脱水更严重，且粪便中带血的情况更频繁。组织学上，肠道E-钙黏蛋白缺乏与急性和慢性炎症加剧以及再生上皮变化增加有关。最后，上皮细胞的变化在E-钙黏蛋白缺乏的小鼠中分布更广泛，而黏膜损伤在对照动物中更局限于局部。
我们的研究结果表明，E-钙黏蛋白可能在溃疡性结肠炎（炎症性肠病的主要临床形式之一）的发病机制中发挥重要作用。
